Public Release: 

Molecular Deficiency Appears To Play Key Role In Muscle Diseases

University of Illinois at Urbana-Champaign

CHAMPAIGN, Ill. -- A molecule discovered on muscle tissue in a University of Illinois laboratory 13 years ago now appears to have pivotal roles in both embryonic muscle formation and in muscle stabilization later in children and adults.

A deficiency of the molecule -- known as the Alpha 7 integrin -- was positively linked to three cases of congenital muscular dystrophy. The finding was discussed in a paper published in the May 19 issue of Nature Genetics.

That finding and accumulating evidence on the multifaceted roles of the Alpha 7 integrin may have significant implications in the understanding of numerous other forms of muscle diseases and in potential therapies, said Stephen J. Kaufman, a professor of cell and structural biology at the U. of I. The integrin was discovered in 1985 in Kaufman's lab and has since been the focus of his research.

Kaufman was one of 17 authors from eight U.S. and Japanese research institutions involved in the Nature Genetics report. He and Dean J. Burkin, a postdoctoral researcher in cell and structural biology, have written a comprehensive review article on the role of the Alpha 7 integrin in muscle development and disease. It will be published in the journal Cell and Tissue Research.

Kaufman's work -- funded by the Muscular Dystrophy Association of America and the National Institutes of Health -- began as basic research on skeletal muscle formation and has evolved into asking what happens when things go wrong with muscle integrity. Kaufman now believes that the integrin may be "a very important player in the very early steps of muscle development, including the formation of neuromuscular and myotendinous junctions."

"We believe it is important for the formation and integrity of these junctional sites," he said. "It also is found between muscle fibers, where it 'glues' fibers together. This integrin also serves as an adhesive agent in different stages of development."

One focus of his research is to resolve how one molecule does so many different things. According to his findings to date, the answer rests in part with the ability of the cell to generate similar but distinct structural and functional forms of the same integrin. "Given all the functions of this molecule," he said, "it is not surprising that there might be problems when different forms are made or not made at all. What is equally intriguing is an excess of this integrin may also be advantageous."

Such may be the case in Duchenne muscular dystrophy, in which a defective gene fails to produce the protein dystrophin. Kaufman and his colleagues have determined that in the absence of dystrophin more of the Alpha 7 integrin is found in the affected muscle fibers.

"The overproduction may lessen the severity of the disease and prolong the time course of the muscle breakdown that occurs," Kaufman said. "We are testing this experimentally to see if raising these levels even more will provide greater protection."


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